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Myrcludex B in Combination With Peginterferon Alfa-2a Versus Peginterferon Alfa-2a Alone in Patients With Chronic Viral Hepatitis B With Delta-agent

Sponsor
Hepatera Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT02888106
Collaborator
(none)
90
Enrollment
7
Locations
6
Arms
55
Actual Duration (Months)
12.9
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Randomised, Comparative, Parallel-Arm Study to Assess Efficacy and Safety of Myrcludex B in Combination with Peginterferon Alfa-2a Versus Peginterferon Alfa-2a Alone in Patients with Chronic Viral Hepatitis B with Delta-agent

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a multicenter, open-label, randomised, comparative, active-controlled parallel-arm phase II study.

The study will be conducted in Russia. The aim of this study is to explore the safety and efficacy of treatment with Myrcludex B used as a monotherapy and in combination with PEG-IFNα and Tenofovir compared to monotherapy with PEG-IFNα in patients with chronic viral hepatitis B with delta-agent, based on the achievement of undetectable viral load at the end of the follow-up period 6 months (24 weeks) after the end of treatment. The study is also aimed at investigating immunogenicity of Myrcludex B and the drug pharmacokinetics when used in combination with PEG IFN alfa-2a and with Tenofovir.

It is planned to screen 110 patients, and 90 patients will be randomised in equal numbers into six treatment arms.

  • Arm A (n=15): PEG IFN alfa-2a 180 µg for 48 weeks

  • Arm B (n=15): Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks

  • Arm C (n=15): Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks

  • Arm D (n=15): Myrcludex B 2 mg for 48 weeks

  • Arm E (n=15): Myrcludex B 10 mg (10 mg once a day)+ PEG IFN alfa-2a 180 µg for 48 weeks

  • Arm F (n=15): Myrcludex B 10 mg (5 mg twice a day)+ Tenofovir for 48 weeks

Study Design

Study Type:
Interventional
Actual Enrollment :
90 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Multicenter, Open-label, Randomized, Comparative, parallel-arm phase II studyMulticenter, Open-label, Randomized, Comparative, parallel-arm phase II study
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-label, Randomised, Comparative, Parallel-Arm, Phase II Study to Assess Efficacy and Safety of Myrcludex B in Combination With Peginterferon Alfa-2a Versus Peginterferon Alfa-2a Alone in Patients With Chronic Viral Hepatitis B With Delta-agent
Actual Study Start Date :
Apr 1, 2016
Actual Primary Completion Date :
Nov 22, 2019
Actual Study Completion Date :
Oct 30, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm A

PEG IFN alfa-2a 180 µg for 48 weeks

Drug: PEG IFN alfa-2a
solution for subcutaneous injection, once per week
Other Names:
  • Pegasys

    		•
    Experimental: Arm B

    Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks

    Drug: Myrcludex B
    Lyophilised powder for solution for subcutaneous injection
    Other Names:
  • Bulevirtide

    • Drug: PEG IFN alfa-2a
    solution for subcutaneous injection, once per week
    Other Names:
  • Pegasys

    		•
    Experimental: Arm C

    Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks

    Drug: Myrcludex B
    Lyophilised powder for solution for subcutaneous injection
    Other Names:
  • Bulevirtide

    • Drug: PEG IFN alfa-2a
    solution for subcutaneous injection, once per week
    Other Names:
  • Pegasys

    		•
    Experimental: Arm D

    Myrcludex B 2 mg for 48 weeks

    Drug: Myrcludex B
    Lyophilised powder for solution for subcutaneous injection
    Other Names:
  • Bulevirtide

    		•
    Experimental: Arm E

    Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks

    Drug: Myrcludex B
    Lyophilised powder for solution for subcutaneous injection
    Other Names:
  • Bulevirtide

    • Drug: PEG IFN alfa-2a
    solution for subcutaneous injection, once per week
    Other Names:
  • Pegasys

    		•
    Experimental: Arm F

    Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks

    Drug: Myrcludex B
    Lyophilised powder for solution for subcutaneous injection
    Other Names:
  • Bulevirtide

    • Drug: Tenofovir
    Film-coated tablets, 300 mg, per os, once daily
    Other Names:
  • Viread

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Patients With Negative HDV RNA by PCR [72 weeks]

      Negativation of HDV RNA by PCR (undetectable HDV RNA) at Week 72 (end of follow-up period)

    Secondary Outcome Measures

    1. Percentage of Patients With Negative HDV RNA by PCR [24 and 48 weeks]

      Percentage of patients with negative HDV RNA by PCR (undetectable HDV RNA) at Weeks 24 and 48

    2. Percentage of Patients With Normalized ALT [24, 48 and 72 weeks]

      Percentage of patients with normalized ALT at Weeks 24, 48 and 72. ALT normalisation was defined as having an ALT value within the normal range (≤31 U/L for females and ≤41 U/L for males)

    3. Percentage of Patients With Combined Response [24, 48 and 72 weeks]

      Combined response is defined as negative HDV RNA and ALT normalization at Weeks 24, 48, and 72. The criteria for combined response were HDV RNA value below LLoD (where LLoD=10 IU/ml) and ALT within normal range (≤31 U/L for females and ≤41 U/L for males)

    4. Percentage of Patients With HВsAg Response [24, 48 and 72 weeks]

      HВsAg response was defined as HBsAg negativation or > 1 log10 IU/mL decline from baseline.

    5. Percentage of Patients With HBsAg Negativation [48 and 72 weeks]

      Undetectable HВsAg with appearance of HbsAg antibodies or without it.

    6. Percentage of Patients With Negative HBV DNA by PCR [24, 48 and 72 weeks]

      Percentage of patients with undetectable HBV DNA by PCR at Weeks 24, 48 and 72

    7. The Intensity of Liver Fibrosis Based on Results of Transient Elastometry of Liver at Weeks 48 and 72. [48 and 72 weeks]

      Change in liver stiffness and intensity of liver fibrosis based on results of transient elastometry of liver at weeks 48 and 72.

    8. Number of Participants With Change (Improvement / Worsening) in Fibrosis and Histological Activity Stage From Baseline to Post-treatment [72 weeks]

      Change (improvement/ worsening) in fibrosis and histological activity stage according to the liver biopsy study results from baseline to post-treatment Liver fibrosis was evaluated by histological staging systems with stage 0 corresponding to absence of fibrosis and with the highest score (the last stage in all systems) corresponding to cirrhosis. Improvement is defined as a decrease of at least 1 point in histological staging systems; worsening is defined as an increase of at least 1 point. Data should be interpreted with caution due to low number of paired biopsies available.

    9. Change in Molecular Analyses of Relative HDV RNA Expression, Relative HBV Pregenomic Expression, Relative Total HBV RNA Expression (X Region), Relative HBV RNA Expression (S Region). [48 and 72 weeks]

      Molecular analyses of relative HDV RNA expression, relative HBV pregenomic expression, relative total HBV RNA expression (X region), relative HBV RNA expression (S region) from baseline to post-treatment. *Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.

    10. Change in Molecular Analyses of Total HBV DNA (X Region) Copies/Cell, HBV DNA (S Region) Copies/Cell, cccDNA Copies/Cell From Baseline to Post-treatment. [48 and 72 weeks]

      Molecular analyses of total HBV DNA (X region) copies/cell, HBV DNA (S region) copies/cell, cccDNA copies/cell from baseline to post-treatment. *Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.

    11. Change in Molecular Analysis of HDAg Positive Hepatocytes (%) From Baseline to Post-treatment [48 and 72 weeks]

      Molecular analysis of HDAg positive Hepatocytes (percentage of HDAg positive Hepatocytes) from baseline to post-treatment. *Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.

    12. Change in the Gene Expression Analyses From Baseline to Post-treatment [Weeks 48 - 72]

      Change in the gene expression analyses of CXCL10, NTCP, CYP7A1, ISG15, MX1, OAS, HLA-E, TAP1 and USP18 from baseline to post-treatment. Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Signed Informed Consent form.

    2. Males and females 18 to 65 years of age (inclusively).

    3. Patients with chronic hepatitis B (HBeAg-positive or negative) and HBsAg-positive for at least 6 months prior to Screening.

    4. Positive for anti-HDV antibodies for at least 6 months prior to Screening.

    5. HDV RNA-positive at Screening.

    6. ALT ≥ 1 x ULN and < 10 x ULN.

    7. The patient agreed to use adequate method of contraception during the study, starting from the time of Informed Consent signing and until completion of the Follow-up Period.

    Exclusion Criteria:

    1. Intolerance or hypersensitivity to the active ingredient or other components of the study drug Myrcludex B.

    2. Intolerance or hypersensitivity to interferons alfa, genetically engineered E.coli medications, polyethylene glycol or other components of peginterferon alfa-2a.

    3. Previous treatment with Myrcludex B (patients with previous exposure to interferon are eligible).

    4. Therapy with antiviral drugs for chronic viral hepatitis B with delta-agent over the previous 6 months.

    5. Therapy with anti-tumour agents (including radiotherapy) or immunomodulatory medications (including systemic glucocorticoids) over the previous 6 months.

    6. The following laboratory test results at Screening:

    7. Hemoglobin < 100 g/L

    8. Leucocytes < 3000/µL

    9. Neutrophils < 1500/µL

    10. Platelets < 90000/µL

    11. Serum creatinine >1.5 x ULN.

    12. Total bilirubin > 34.2 µM/L. Patients with higher total bilirubin may be enrolled upon consultation with the study Medical Monitor, if there is clear evidence that the elevated bilirubin is caused by Gilbert's syndrome.

    13. Current or previous decompensated liver disease, including coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminaemia, ascites, and oesophageal varices haemorrhage; Child-Pugh score of B/C or ≥6 points.

    14. HCV or HIV coinfection (patients with anti-HCV antibodies and no HCV RNA at Screening are eligible).

    15. Hepatocellular carcinoma.

    16. Signs of drug- or alcohol-induced liver disease or any other medical conditions associated with chronic liver disease (e.g. autoimmune hepatitis, hemochromatosis, thalassaemia, alcoholic hepatitis, toxic liver disease).

    17. Contraindications for liver biopsy.

    18. Concurrent malignancy (current diagnosed or suspected malignancy; risk of a previous malignancy recurrence).

    19. Severe decompensated cardiovascular diseases, including unstable and poorly controlled conditions, over 6 months before Screening.

    20. History of poorly controlled thyroid conditions or clinically significant signs of thyroid dysfunction at Screening.

    21. Previous or current severe renal failure or significant renal dysfunction at Screening.

    22. Previous or current chronic pulmonary disease with respiratory distortion at Screening.

    23. Previous or current severe retinopathy, significant ophthalmology disorders associated with diabetes mellitus or hypertension.

    24. Previous or current severe psychiatric disorders at Screening (e.g. severe depressions, suicidal attempts, severe neuroses or cognitive disorders).

    25. Previous or current endocrine disorders (hypoglycaemia, hyperglycaemia, diabetes mellitus) that are not adequately controlled at Screening.

    26. History of visceral organ transplantation.

    27. Signs of drug and/or alcohol dependence (80 g of alcohol/day for men and 40 g of alcohol/day for women) within 1 year before Screening.

    28. History of immune disorders (e.g. idiopathic thrombocytopenic purpura, lupus erythematosus, sclerodermia, severe psoriasis, rheumatoid arthritis).

    29. Need for concomitant use of glucocorticoids or myelotoxic agents.

    30. Participation in another clinical study within 30 days prior to enrollment into this study.

    31. Pregnant or breast-feeding females.

    32. Any other condition that, in the opinion of Investigator, precludes the patient from taking part in this study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 State Budgetary educational institution of higher professional education "South Ural State Medical University" Ministry of healthcare Chelyabinsk Russian Federation
    2 State Budgetary Institution of healthcare "Specialized Clinical Infectious Diseases Hospital" Ministry of Health Krasnodar Russian Federation
    3 Moscow Regional Research and Clinical Institute Moscow Russian Federation 129110
    4 Federal Budget Institution of Science "Central Research Institute of Epidemiology" of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance Moscow Russian Federation
    5 LLC "Clinic of Modern Medicine" Moscow Russian Federation
    6 Medical Company "Gepatolog" LLC Samara Russian Federation
    7 State Budgetary Institution of healthcare 'Stavropol regional clinical hospital' Stavropol' Russian Federation

    Sponsors and Collaborators

    • Hepatera Ltd.

    Investigators

    • Principal Investigator: Pavel Bogomolov, PhD, Moscow Regional Research and Clinical Institute Moniki n.a. M.F. Vladimirskiy

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Hepatera Ltd.
    ClinicalTrials.gov Identifier:
    NCT02888106
    Other Study ID Numbers:
    • MYR 203
    First Posted:
    Sep 2, 2016
    Last Update Posted:
    Apr 30, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis B, Chronic
    Hepatitis
    Tenofovir
    Peginterferon alfa-2a
    Interferon alpha-2

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Period Title: Overall Study
    STARTED 15 15 15 15 15 15
    COMPLETED 10 13 15 13 14 14
    NOT COMPLETED 5 2 0 2 1 1

    Baseline Characteristics

    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F Total
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks Total of all reporting groups
    Overall Participants 15 15 15 15 15 15 90
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    15
    100%
    15
    100%
    15
    100%
    15
    100%
    15
    100%
    15
    100%
    90
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    34.1
    (7.0)
    37.1
    (5.5)
    36.9
    (7.5)
    42.0
    (9.6)
    36.2
    (7.2)
    34.3
    (7.2)
    36.8
    (7.7)
    Sex: Female, Male (Count of Participants)
    Female
    10
    66.7%
    4
    26.7%
    8
    53.3%
    4
    26.7%
    3
    20%
    4
    26.7%
    33
    36.7%
    Male
    5
    33.3%
    11
    73.3%
    7
    46.7%
    11
    73.3%
    12
    80%
    11
    73.3%
    57
    63.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    6.7%
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    2
    2.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    14
    93.3%
    15
    100%
    15
    100%
    15
    100%
    14
    93.3%
    15
    100%
    88
    97.8%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Russia
    15
    100%
    15
    100%
    15
    100%
    15
    100%
    15
    100%
    15
    100%
    90
    100%
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    168.9
    (6.8)
    172.5
    (9.4)
    171.4
    (6.0)
    174.6
    (8.6)
    174.1
    (8.2)
    173.5
    (6.8)
    172.5
    (7.7)
    Body Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    68.02
    (14.61)
    74.29
    (14.44)
    72.37
    (11.55)
    82.95
    (16.38)
    72.67
    (10.01)
    70.53
    (9.08)
    73.47
    (13.43)
    Body Mass Idex (kg/m²) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m²]
    23.77
    (4.68)
    24.83
    (3.46)
    24.69
    (4.18)
    27.02
    (3.91)
    24.03
    (3.21)
    23.48
    (3.31)
    24.64
    (3.90)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Patients With Negative HDV RNA by PCR
    Description Negativation of HDV RNA by PCR (undetectable HDV RNA) at Week 72 (end of follow-up period)
    Time Frame 72 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 15 15 15 15 15 15
    Number (95% Confidence Interval) [Percentage of participants]
    0
    0%
    53.3
    355.3%
    26.7
    178%
    6.7
    44.7%
    6.7
    44.7%
    33.3
    222%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments The proportions of negative HDV RNA response at week 72 in each of the MXB treatment groups were compared with the control group of PEG-IFNα by using Fisher's exact test and by presenting exact unconditional 95%-confidence intervals (CI) based on scores for the proportion differences.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0022
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0996
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0421
    Comments
    Method Fisher Exact
    Comments
    2. Secondary Outcome
    Title Percentage of Patients With Negative HDV RNA by PCR
    Description Percentage of patients with negative HDV RNA by PCR (undetectable HDV RNA) at Weeks 24 and 48
    Time Frame 24 and 48 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 15 15 15 15 15 15
    Week 24
    6.7
    44.7%
    60.0
    400%
    60.0
    400%
    13.3
    88.7%
    66.7
    444.7%
    26.7
    178%
    Week 48
    13.3
    88.7%
    80.0
    533.3%
    86.7
    578%
    13.3
    88.7%
    80
    533.3%
    46.7
    311.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0052
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0052
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0017
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3295
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0007
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0007
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1086
    Comments
    Method Fisher Exact
    Comments
    3. Secondary Outcome
    Title Percentage of Patients With Normalized ALT
    Description Percentage of patients with normalized ALT at Weeks 24, 48 and 72. ALT normalisation was defined as having an ALT value within the normal range (≤31 U/L for females and ≤41 U/L for males)
    Time Frame 24, 48 and 72 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 15 15 15 15 15 15
    Week 24
    0
    0%
    6.7
    44.7%
    20.0
    133.3%
    64.3
    428.7%
    20.0
    133.3%
    60.0
    400%
    Week 48
    26.7
    178%
    26.7
    178%
    46.7
    311.3%
    73.3
    488.7%
    26.7
    178%
    40.0
    266.7%
    Week 72
    10.0
    66.7%
    53.8
    358.7%
    33.3
    222%
    23.1
    154%
    35.7
    238%
    35.7
    238%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2241
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2241
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0007
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4497
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0268
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6999
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Arm A
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0743
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3449
    Comments
    Method t-test, 1 sided
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6036
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3408
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3408
    Comments
    Method Fisher Exact
    Comments
    4. Secondary Outcome
    Title Percentage of Patients With Combined Response
    Description Combined response is defined as negative HDV RNA and ALT normalization at Weeks 24, 48, and 72. The criteria for combined response were HDV RNA value below LLoD (where LLoD=10 IU/ml) and ALT within normal range (≤31 U/L for females and ≤41 U/L for males)
    Time Frame 24, 48 and 72 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 15 15 15 15 15 15
    Week 24
    0
    0%
    6.7
    44.7%
    20.0
    133.3%
    13.3
    88.7%
    13.3
    88.7%
    13.3
    88.7%
    Week 48
    6.7
    44.7%
    20.0
    133.3%
    33.3
    222%
    13.3
    88.7%
    20.0
    133.3%
    13.3
    88.7%
    Week 72
    0
    0%
    46.7
    311.3%
    13.3
    88.7%
    6.7
    44.7%
    6.7
    44.7%
    13.3
    88.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2241
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5977
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1686
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5977
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0063
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments
    Method Fisher Exact
    Comments
    5. Secondary Outcome
    Title Percentage of Patients With HВsAg Response
    Description HВsAg response was defined as HBsAg negativation or > 1 log10 IU/mL decline from baseline.
    Time Frame 24, 48 and 72 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 15 15 15 15 15 15
    Week 24
    6.7
    44.7%
    40.0
    266.7%
    13.3
    88.7%
    0
    0%
    6.7
    44.7%
    6.7
    44.7%
    Week 48
    0
    0%
    46.7
    311.3%
    20.0
    133.3%
    0
    0%
    6.7
    44.7%
    0
    0%
    Week 72
    0
    0%
    40.0
    266.7%
    13.3
    88.7%
    0
    0%
    13.3
    88.7%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0801
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0063
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2241
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0169
    Comments
    Method Regression, Cox
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments
    Method Fisher Exact
    Comments
    6. Secondary Outcome
    Title Percentage of Patients With HBsAg Negativation
    Description Undetectable HВsAg with appearance of HbsAg antibodies or without it.
    Time Frame 48 and 72 weeks

    Outcome Measure Data

    Analysis Population Description
    According to SAP Section 7.1.5 - Handling of missing data.
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 15 15 15 15 15 15
    Week 48 HBsAg negativation with appearance of HbsAg antibodies
    0
    0%
    13.3
    88.7%
    0
    0%
    0
    0%
    6.7
    44.7%
    0
    0%
    Week 72 HBsAg negativation with appearance of HbsAg antibodies
    0
    0%
    23.1
    154%
    0
    0%
    0
    0%
    7.1
    47.3%
    0
    0%
    Week 48 HBsAg negativation without appearance of HbsAg antibodies
    0
    0%
    6.7
    44.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Week 72 HBsAg negativation without appearance of HbsAg antibodies
    0
    0%
    7.7
    51.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2292
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    7. Secondary Outcome
    Title Percentage of Patients With Negative HBV DNA by PCR
    Description Percentage of patients with undetectable HBV DNA by PCR at Weeks 24, 48 and 72
    Time Frame 24, 48 and 72 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 15 15 15 15 15 15
    Week 24
    33.3
    222%
    53.3
    355.3%
    40.0
    266.7%
    33.3
    222%
    53.3
    355.3%
    80.0
    533.3%
    Week 48
    26.7
    178%
    73.3
    488.7%
    40.0
    266.7%
    33.3
    222%
    66.7
    444.7%
    93.3
    622%
    Week 72
    33.3
    222%
    66.7
    444.7%
    40.0
    266.7%
    40.0
    266.7%
    26.7
    178%
    46.7
    311.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4621
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Chi-squared, Corrected
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4621
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0253
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0268
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6999
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0656
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0005
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1431
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm D
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm E
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.0000
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Arm A, Arm F
    Comments Week 72
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7104
    Comments
    Method Fisher Exact
    Comments
    8. Secondary Outcome
    Title The Intensity of Liver Fibrosis Based on Results of Transient Elastometry of Liver at Weeks 48 and 72.
    Description Change in liver stiffness and intensity of liver fibrosis based on results of transient elastometry of liver at weeks 48 and 72.
    Time Frame 48 and 72 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks PEG IFN alfa-2a: solution for subcutaneous injection, once per week Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B: Lyophilised powder for solution for subcutaneous injection PEG IFN alfa-2a: solution for subcutaneous injection, once per week Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B: Lyophilised powder for solution for subcutaneous injection PEG IFN alfa-2a: solution for subcutaneous injection, once per week Myrcludex B 2 mg for 48 weeks Myrcludex B: Lyophilised powder for solution for subcutaneous injection Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B: Lyophilised powder for solution for subcutaneous injection PEG IFN alfa-2a: solution for subcutaneous injection, once per week Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks Myrcludex B: Lyophilised powder for solution for subcutaneous injection Tenofovir: Film-coated tablets, 300 mg, per os, once daily
    Measure Participants 13 13 14 9 15 15
    Change from baseline to Week 48
    -0.67
    (2.78)
    1.97
    (3.94)
    -0.27
    (3.83)
    -0.66
    (2.52)
    -2.35
    (7.47)
    -1.12
    (3.23)
    Change from baseline to Week 72
    -0.67
    (5.25)
    0.65
    (2.10)
    -2.06
    (4.49)
    0.00
    (6.19)
    0.21
    (6.53)
    -1.20
    (2.68)
    9. Secondary Outcome
    Title Number of Participants With Change (Improvement / Worsening) in Fibrosis and Histological Activity Stage From Baseline to Post-treatment
    Description Change (improvement/ worsening) in fibrosis and histological activity stage according to the liver biopsy study results from baseline to post-treatment Liver fibrosis was evaluated by histological staging systems with stage 0 corresponding to absence of fibrosis and with the highest score (the last stage in all systems) corresponding to cirrhosis. Improvement is defined as a decrease of at least 1 point in histological staging systems; worsening is defined as an increase of at least 1 point. Data should be interpreted with caution due to low number of paired biopsies available.
    Time Frame 72 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 4 4 4 7 5 14
    Improvement
    0
    0%
    0
    0%
    1
    6.7%
    4
    26.7%
    3
    20%
    8
    53.3%
    No change
    2
    13.3%
    0
    0%
    3
    20%
    2
    13.3%
    1
    6.7%
    2
    13.3%
    Worsening
    2
    13.3%
    4
    26.7%
    0
    0%
    1
    6.7%
    1
    6.7%
    4
    26.7%
    Improvement
    0
    0%
    0
    0%
    1
    6.7%
    3
    20%
    1
    6.7%
    7
    46.7%
    No change
    2
    13.3%
    0
    0%
    3
    20%
    2
    13.3%
    3
    20%
    3
    20%
    Worsening
    2
    13.3%
    4
    26.7%
    0
    0%
    2
    13.3%
    1
    6.7%
    4
    26.7%
    Improvement
    0
    0%
    0
    0%
    1
    6.7%
    4
    26.7%
    1
    6.7%
    7
    46.7%
    No change
    2
    13.3%
    1
    6.7%
    3
    20%
    2
    13.3%
    3
    20%
    3
    20%
    Worsening
    2
    13.3%
    3
    20%
    0
    0%
    1
    6.7%
    1
    6.7%
    4
    26.7%
    Improvement
    1
    6.7%
    1
    6.7%
    2
    13.3%
    6
    40%
    1
    6.7%
    8
    53.3%
    No change
    2
    13.3%
    1
    6.7%
    2
    13.3%
    1
    6.7%
    3
    20%
    5
    33.3%
    Worsening
    1
    6.7%
    2
    13.3%
    0
    0%
    0
    0%
    1
    6.7%
    1
    6.7%
    Improvement
    2
    13.3%
    1
    6.7%
    2
    13.3%
    6
    40%
    2
    13.3%
    9
    60%
    No change
    0
    0%
    0
    0%
    2
    13.3%
    1
    6.7%
    1
    6.7%
    1
    6.7%
    Worsening
    2
    13.3%
    3
    20%
    0
    0%
    0
    0%
    2
    13.3%
    4
    26.7%
    10. Secondary Outcome
    Title Change in Molecular Analyses of Relative HDV RNA Expression, Relative HBV Pregenomic Expression, Relative Total HBV RNA Expression (X Region), Relative HBV RNA Expression (S Region).
    Description Molecular analyses of relative HDV RNA expression, relative HBV pregenomic expression, relative total HBV RNA expression (X region), relative HBV RNA expression (S region) from baseline to post-treatment. *Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.
    Time Frame 48 and 72 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 4 4 3 6 5 14
    Relative HDV RNA expression
    -0.062
    (0.097)
    -0.068
    (0.145)
    0.296
    (0.652)
    -1.220
    (1.285)
    -1.676
    (2.754)
    -0.975
    (1.732)
    Relative HBV pregenomic expression
    -0.028
    (0.044)
    -0.004
    (0.007)
    0.003
    (0.010)
    -0.001
    (0.006)
    -0.041
    (0.101)
    0.049
    (0.257)
    Relative total HBV RNA expression (X region)
    0.080
    (1.070)
    -1.088
    (1.624)
    -1.295
    (0.511)
    -0.282
    (0.796)
    0.160
    (1.380)
    0.403
    (1.477)
    Relative HBV RNA expression (S region)
    -0.688
    (1.977)
    -2.295
    (2.306)
    -1.696
    (1.423)
    -0.451
    (0.962)
    0.223
    (1.909)
    0.733
    (2.372)
    11. Secondary Outcome
    Title Change in Molecular Analyses of Total HBV DNA (X Region) Copies/Cell, HBV DNA (S Region) Copies/Cell, cccDNA Copies/Cell From Baseline to Post-treatment.
    Description Molecular analyses of total HBV DNA (X region) copies/cell, HBV DNA (S region) copies/cell, cccDNA copies/cell from baseline to post-treatment. *Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.
    Time Frame 48 and 72 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 4 4 3 6 5 14
    Total HBV DNA (X region) copies/cell
    -0.041
    (0.215)
    -0.027
    (0.452)
    -0.132
    (0.223)
    0.036
    (0.240)
    -0.297
    (0.874)
    0.087
    (0.156)
    HBV DNA (S region) copies/cell
    -0.413
    (0.784)
    -0.944
    (1.265)
    -0.747
    (1.149)
    0.124
    (0.954)
    -1.545
    (3.047)
    0.196
    (0.517)
    cccDNA copies/cell
    -0.045
    (0.083)
    0.030
    (0.050)
    0.004
    (0.042)
    -0.003
    (0.200)
    -0.117
    (0.194)
    0.058
    (0.165)
    12. Secondary Outcome
    Title Change in Molecular Analysis of HDAg Positive Hepatocytes (%) From Baseline to Post-treatment
    Description Molecular analysis of HDAg positive Hepatocytes (percentage of HDAg positive Hepatocytes) from baseline to post-treatment. *Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.
    Time Frame 48 and 72 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 4 3 2 5 5 14
    Baseline
    0.757
    (0.873)
    2.178
    (3.275)
    1.209
    (1.001)
    7.550
    (7.905)
    12.521
    (13.855)
    3.641
    (5.919)
    Change from baseline to post-treatment
    0.099
    (NA)
    -1.961
    (3.439)
    -1.134
    (0.995)
    -10.334
    (9.041)
    -9.028
    (16.100)
    -3.616
    (5.923)
    13. Secondary Outcome
    Title Change in the Gene Expression Analyses From Baseline to Post-treatment
    Description Change in the gene expression analyses of CXCL10, NTCP, CYP7A1, ISG15, MX1, OAS, HLA-E, TAP1 and USP18 from baseline to post-treatment. Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.
    Time Frame Weeks 48 - 72

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    Measure Participants 4 4 3 4 5 14
    CXCL10 relative expression
    -0.017
    (0.033)
    -0.012
    (0.019)
    0.010
    (0.005)
    -0.034
    (0.009)
    0.003
    (0.062)
    -0.015
    (0.017)
    NTCP relative expression
    0.001
    (0.010)
    -0.016
    (0.012)
    0.001
    (0.004)
    0.002
    (0.005)
    0.011
    (0.008)
    0.004
    (0.008)
    CYP7A1 relative expression
    0.002
    (0.006)
    0.002
    (0.006)
    0.000
    (0.001)
    0.001
    (0.002)
    -0.001
    (0.002)
    0.001
    (0.003)
    ISG15 relative expression
    0.207
    (0.160)
    -0.092
    (0.321)
    -0.003
    (0.004)
    -0.037
    (0.024)
    -0.163
    (0.286)
    -0.005
    (0.034)
    MX1 relative expression
    0.175
    (0.141)
    -0.020
    (0.186)
    -0.013
    (0.014)
    -0.034
    (0.019)
    -0.056
    (0.122)
    -0.000
    (0.026)
    OAS relative expression
    0.067
    (0.059)
    -0.019
    (0.063)
    0.005
    (0.009)
    -0.015
    (0.010)
    -0.025
    (0.049)
    0.003
    (0.014)
    HLA-E relative expression
    0.038
    (0.095)
    -0.322
    (0.175)
    0.015
    (0.179)
    -0.386
    (0.197)
    0.149
    (0.308)
    -0.061
    (0.191)
    TAP1 relative expression
    0.000
    (0.007)
    -0.012
    (0.008)
    -0.001
    (0.004)
    -0.017
    (0.009)
    0.007
    (0.019)
    -0.004
    (0.007)
    USP18 relative expression
    0.021
    (0.017)
    -0.003
    (0.016)
    -0.003
    (0.006)
    -0.005
    (0.004)
    -0.002
    (0.012)
    0.001
    (0.003)

    Adverse Events

    Time Frame 72 weeks
    Adverse Event Reporting Description
    Arm/Group Title Arm A Arm B Arm C Arm D Arm E Arm F
    Arm/Group Description PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks Myrcludex B 2 mg for 48 weeks Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks
    All Cause Mortality
    Arm A Arm B Arm C Arm D Arm E Arm F
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%)
    Serious Adverse Events
    Arm A Arm B Arm C Arm D Arm E Arm F
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 1/15 (6.7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%)
    Gastrointestinal disorders
    Anal fistula /15 (NaN) 1/15 (6.7%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1
    Proctitis /15 (NaN) 1/15 (6.7%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1
    Other (Not Including Serious) Adverse Events
    Arm A Arm B Arm C Arm D Arm E Arm F
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/15 (86.7%) 14/15 (93.3%) 14/15 (93.3%) 15/15 (100%) 15/15 (100%) 15/15 (100%)
    Blood and lymphatic system disorders
    Neutripenia 8/15 (53.3%) 32 10/15 (66.7%) 28 9/15 (60%) 28 3/15 (20%) 6 14/15 (93.3%) 57 3/15 (20%) 12
    Thrombocytopenia 8/15 (53.3%) 16 11/15 (73.3%) 23 7/15 (46.7%) 18 3/15 (20%) 7 12/15 (80%) 29 5/15 (33.3%) 14
    Lymphopenia 5/15 (33.3%) 12 1/15 (6.7%) 1 1/15 (6.7%) 2 1/15 (6.7%) 1 5/15 (33.3%) 10 2/15 (13.3%) 2
    Anaemia 3/15 (20%) 6 2/15 (13.3%) 4 1/15 (6.7%) 1 0/15 (0%) 0 3/15 (20%) 3 1/15 (6.7%) 1
    Reticulocytopenia 5/15 (33.3%) 12 0/15 (0%) 0 1/15 (6.7%) 2 2/15 (13.3%) 2 0/15 (0%) 0 0/15 (0%) 0
    Erythropenia 4/15 (26.7%) 7 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Reticulocytosis 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 4 2/15 (13.3%) 3 1/15 (6.7%) 2
    Monocytopenia 3/15 (20%) 5 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Monocytosis 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0
    Neutrophilia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0
    Eosinophilia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Splenic calcification 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Cardiac disorders
    Bradycardia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 3
    Tachycardia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Ear and labyrinth disorders
    Ear pain 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 3
    Eye disorders
    Chalazion 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Gastrointestinal disorders
    Nausea 4/15 (26.7%) 6 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 2
    Proctalgia 0/15 (0%) 0 1/15 (6.7%) 4 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Diarrhoea 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2
    Gingival bleeding 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0
    Dry mouth 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Abdominal discomfort 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Abdominal distension 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Abdominal pain upper 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Dyspepsia 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Pancreatitis chronic 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Toothache 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    General disorders
    Influenza like illness 1/15 (6.7%) 1 9/15 (60%) 11 8/15 (53.3%) 8 0/15 (0%) 0 3/15 (20%) 4 0/15 (0%) 0
    Asthenia 3/15 (20%) 3 3/15 (20%) 3 5/15 (33.3%) 5 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 3
    Hyperthermia 7/15 (46.7%) 26 0/15 (0%) 0 1/15 (6.7%) 5 1/15 (6.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0
    Injection site erythema 1/15 (6.7%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 3/15 (20%) 8 1/15 (6.7%) 2
    Pyrexia 1/15 (6.7%) 1 1/15 (6.7%) 1 3/15 (20%) 3 0/15 (0%) 0 3/15 (20%) 6 0/15 (0%) 0
    Fatigue 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0
    Chills 1/15 (6.7%) 1 1/15 (6.7%) 3 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Injection site haematoma 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1
    Injection site reaction 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1
    Xerosis 1/15 (6.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Chest pain 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 3 0/15 (0%) 0 0/15 (0%) 0
    Injection site bruising 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Injection site induration 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Injection site pruritus 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1
    Thirst 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Hepatobiliary disorders
    Hyperbilirubineamia 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 1/15 (6.7%) 4 3/15 (20%) 7 2/15 (13.3%) 4
    Cholelithiasis 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Gallbladder polyp 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1
    Hepatic calcification 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Hepatic cirrhosis 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Jaundice 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Liver disorder 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Infections and infestations
    Respiratory track infection 1/15 (6.7%) 1 2/15 (13.3%) 2 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Respiratory track infection viral 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 2 0/15 (0%) 0 0/15 (0%) 0
    Sinusitis 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Bronchitis 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Gingivitis 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Herpes zoster 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Purulent discharge 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Injury, poisoning and procedural complications
    Injection related reaction 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0 0/15 (0%) 0
    Investigations
    ALT increased 5/15 (33.3%) 11 5/15 (33.3%) 9 6/15 (40%) 11 8/15 (53.3%) 8 8/15 (53.3%) 24 4/15 (26.7%) 8
    AST increased 5/15 (33.3%) 11 4/15 (26.7%) 8 4/15 (26.7%) 6 8/15 (53.3%) 8 6/15 (40%) 19 4/15 (26.7%) 5
    GGT increased 4/15 (26.7%) 9 4/15 (26.7%) 7 3/15 (20%) 5 4/15 (26.7%) 5 8/15 (53.3%) 16 0/15 (0%) 0
    Haemoglobin decreased 4/15 (26.7%) 5 0/15 (0%) 0 2/15 (13.3%) 2 1/15 (6.7%) 2 1/15 (6.7%) 1 1/15 (6.7%) 1
    Neutrophil count decreased 0/15 (0%) 0 0/15 (0%) 0 3/15 (20%) 6 0/15 (0%) 0 2/15 (13.3%) 8 2/15 (13.3%) 4
    White blood cell count decreased 1/15 (6.7%) 2 0/15 (0%) 0 2/15 (13.3%) 2 0/15 (0%) 0 2/15 (13.3%) 5 1/15 (6.7%) 1
    C-reactive protein increased 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 8 2/15 (13.3%) 4
    Platelet count decreased 1/15 (6.7%) 1 0/15 (0%) 0 3/15 (20%) 6 0/15 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0
    Amylase increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 3/15 (20%) 3 1/15 (6.7%) 1
    Activated partial thromboplastin time prolonged 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 2/15 (13.3%) 4 1/15 (6.7%) 2
    Blood thyroid stimulating hormone decreased 1/15 (6.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1
    Lipase increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 3/15 (20%) 3
    Blood lactate dehydrogenase increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 4 1/15 (6.7%) 2
    Red blood cell sedimentation rate increased 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Weight decreased 1/15 (6.7%) 1 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Haematocrit decreased 1/15 (6.7%) 2 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Reticulocyte count decreased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0 0/15 (0%) 0
    Activated partial thromboplastin time shortened 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1
    Blood bilirubin increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1
    Blood creatinine increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Blood glucose increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Blood lactate dehydrogenase decreased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Blood thyroid stimulating hormone increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Body temperature increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Electrocardiogram abnormal 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Protein total increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Thyroxine increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Urobilinogen urine increased 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Leukopenia 9/15 (60%) 25 8/15 (53.3%) 21 7/15 (46.7%) 19 4/15 (26.7%) 8 14/15 (93.3%) 58 4/15 (26.7%) 12
    Metabolism and nutrition disorders
    Hypocholesterolaemia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 3 2/15 (13.3%) 5
    Hyperlipasaemia 1/15 (6.7%) 3 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 5
    Hypocalcaemia 1/15 (6.7%) 2 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Hyperkalaemia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 1/15 (6.7%) 1
    Decreased appetite 2/15 (13.3%) 2 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Hyperglycaemia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1
    Hyperamylasaemia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 5
    Hypercholesterolaemia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0
    Hypoglycaemia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1
    Hypokalaemia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Hypotriglyceridaemia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Hypertriglyceridaemia 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/15 (6.7%) 4 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Back pain 1/15 (6.7%) 1 1/15 (6.7%) 2 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Myalgia 2/15 (13.3%) 6 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Fybromyalgia 1/15 (6.7%) 2 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Bone pain 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Pain in extremity 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Psoriatic arthropathy 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Haemangioma of liver 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Nervous system disorders
    Headache 3/15 (20%) 8 1/15 (6.7%) 2 2/15 (13.3%) 3 1/15 (6.7%) 1 0/15 (0%) 0 2/15 (13.3%) 3
    Somnolence 2/15 (13.3%) 3 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Dizziness 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Dysgeusia 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Tremor 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Psychiatric disorders
    Insomnia 2/15 (13.3%) 2 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Irritability 2/15 (13.3%) 3 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Apathy 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Depression 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Sleep disorder 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Renal and urinary disorders
    Proteinuria 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 5/15 (33.3%) 7 1/15 (6.7%) 1
    Haematuria 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 3/15 (20%) 4 0/15 (0%) 0
    Urethral pain 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Reproductive system and breast disorders
    Menstrual disorder 2/15 (13.3%) 2 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Epistaxis 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Oropharyngeal pain 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0
    Rhinorrhoea 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 4/15 (26.7%) 4 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Rash 3/15 (20%) 3 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Dry skin 1/15 (6.7%) 1 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1
    Pruritus 2/15 (13.3%) 2 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Hyperhidrosis 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0
    Hidradenitis 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 3 0/15 (0%) 0
    Hand dermatitis 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Nail dystrophy 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Psoriasis 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0
    Vascular disorders
    Hypertension 0/15 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/15 (6.7%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Yana Deloveri
    Organization Hepatera LLC
    Phone +7 495 762 52 53 ext 42-14
    Email deloveri@hepatera.ru
    Responsible Party:
    Hepatera Ltd.
    ClinicalTrials.gov Identifier:
    NCT02888106
    Other Study ID Numbers:
    • MYR 203
    First Posted:
    Sep 2, 2016
    Last Update Posted:
    Apr 30, 2021
    Last Verified:
    Mar 1, 2021